title: Genetic variations of E6 and long control region of human papillomavirus type 16 from patients with cervical lesion in Liaoning, China.
abstract: BACKGROUND
  High-risk human papillomavirus type 16 (HPV16) is a risk factor for cervical cancer. Previous studies suggest that polymorphisms in the E6 gene or the long control region(LCR)of HPV16 may alter the oncogenic potential of the virus. The aims of this study were to investigate the genetic variations of HPV16 E6 gene and LCR in isolates from Chinese population and correlation of the E6 and LCR polymorphisms with disease status of infected patients.
  
  
  METHODS
  HPV16 positive endocervical specimens were collected from 304 women living in Northeast of China. Sequences of E6 gene and LCR were analyzed by PCR-sequencing.
  
  
  RESULTS
  Two lineages were found in the populations, including EUR lineage and As lineage. Based on the HPV16 prototype, the most frequent variation in the E6 gene was T178A/G (48.7%), followed by mutations of G94A (12.2%) and T350G (9.9%). The rank orders of incidence of E6 variations in amino acid were as follows: D25E (46.3%), L83V (9.9%) and H78Y (4.3%). Nucleotide variations in LCR were found in all the 304 isolates from HPV16 positive cervical samples. The most commonly observed LCR variations were the transition replacement G7193T, 7434CIns, G7521A and 7863ADel (100%). The As lineage was associated with HPV persistent infections and with disease status of ≥CIN2,3. The EUR lineage variants showed a negative trend of association with the severity of ≥CIN2,3. Among 41 variations found in LCR, 25 (61.0%) were located at the binding sites for transcription factors. Occurrence of ≥CIN2,3 was significantly associated with the mutations of R10G/L83V in E6 and the C7294T co-variation in LCR, after adjusting for ages of infected patients.
  
  
  CONCLUSIONS
  Associations between As lineage and HPV persistent infections, and with disease status of ≥CIN2,3, and an association between the EUR lineage and negative trend of association with the severity of ≥CIN2,3 were found in this study. An association between a co-variation of R10G/L83V in E6 and C7294T in LCR and an increased risk for developing CIN-2,3 was found in a HPV16 infected population of Chinese women. These findings indicate that HPV16 polymorphism influences development of CIN-2,3.
authors.affiliation: Present address: Virus Laboratory, The Affiliated Shengjing Hospital, China Medical University, No 36, Sanhao Street, Heping District, Shenyang 110004, China. ruanq@sj-hospital.org.
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Lu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.forename: Guili
authors.initials: G
authors.lastname: Wang
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Zhou
authors.forename: Lianxia
authors.initials: L
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ruan
mesh_terms: D000328:Adult; D000368:Aged; D002681:China / Q000453:epidemiology; D004279:DNA, Viral / Q000737:chemistry; D005260:Female; D014644:Genetic Variation; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000150:complications / Q000453:epidemiology / Q000821:virology*; D011110:Polymorphism, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins